The IRAK-ERK-p67phox-Nox-2 axis mediates TLR4, 2-induced ROS production for IL-1β transcription and processing in monocytes

Cellular & Molecular Immunology
Ankita SinghManoj K Barthwal

Abstract

In monocytic cells, Toll-like receptor 4 (TLR4)- and TLR2-induced reactive oxygen species (ROS) cause oxidative stress and inflammatory response; however, the mechanism is not well understood. The present study investigated the role of interleukin-1 receptor-associated kinase (IRAK), extracellular signal-regulated kinase (ERK), p67phox and Nox-2 in TLR4- and TLR2-induced ROS generation during interleukin-1 beta (IL-1β) transcription, processing, and secretion. An IRAK1/4 inhibitor, U0126, PD98059, an NADPH oxidase inhibitor (diphenyleneiodonium (DPI)), and a free radical scavenger (N-acetyl cysteine (NAC))-attenuated TLR4 (lipopolysaccharide (LPS))- and TLR2 (Pam3csk4)-induced ROS generation and IL-1β production in THP-1 and primary human monocytes. An IRAK1/4 inhibitor and siRNA-attenuated LPS- and Pam3csk4-induced ERK-IRAK1 association and ERK phosphorylation and activity. LPS and Pam3csk4 also induced IRAK1/4-, ERK- and ROS-dependent activation of activator protein-1 (AP-1), IL-1β transcription, and IL-1β processing because significant inhibition in AP-1 activity, IL-1β transcription, Pro- and mature IL-β expression, and caspase-1 activity was observed with PD98059, U0126, DPI, NAC, an IRAK1/4 inhibitor, tanshinone IIa, and ...Continue Reading

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Citations

Mar 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zyanya P Espinosa-RiquerClaudia González-Espinosa
Mar 15, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·G V R Krishna PrasadArunika Mukhopadhaya
Jun 21, 2018·Cellular & Molecular Immunology·Priya Gupta, Manoj K Barthwal
Dec 31, 2019·Journal of Neuroinflammation·Xia LiuBing Wang
Dec 9, 2017·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Andrew C SullivanVermont P Dia
Apr 4, 2021·Antioxidants·Štěpánka BenákováLydie Plecitá-Hlavatá
Jun 23, 2020·ACS Pharmacology & Translational Science·Ying ZhouDanielle Kamato

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